3 years ago

FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages

Jianxin Ji, Xin Chen, Xia He, Shuang Chen, Bogang Li
Macrophages are abundant in the tumor microenvironment. They are highly plastic and able to acquire pro-tumoral phenotypes in response to microenvironmental stimuli. When we treated RAW 264.7 macrophages with inhibitors of various oncogenic pathways, we found that the focal adhesion kinase (FAK) inhibitors PF573228 and TAE226 could induce cell multinucleation by suppressing furrowing and cytokinesis. This failure in cytokinesis involves Rac1, whose activity is elevated by FAK inhibitors, and the p21-activated kinases (PAKs), the downstream effectors of Rac. We also investigated the influence of cell multinucleation on macrophage physiology in RAW 264.7 cells. This is the first report that FAK inhibitors suppress furrow ingression and early cytokinesis. Of note, we found that FAK inhibitors cause dramatic increase of pro-tumoral cytokines in multinuclear cells, suggesting the potential to convert macrophages into pro-tumoral cells. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/1873-3468.12895

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